Objectives Develop and test recombinant bacterial vaccines to elicit mucosal immunity to SIV in rhesus. ABSTRACT:Recombinant Salmonella typhimurium strains were engineered to express SIV p27gag protein from a chromosomal construct. Previous studies in mice showed generation of specific cellular immune responses to viral protein when this vaccine was given as live bacteria via oral inoculation. Vaccination of macaques with live recombinant bacteria produced cellular immune responses and as predicted from the murine studies, minimal serum antibody response to viral proteins. Intramuscular injection of purified gag protein was contrasted to oral administration of bacteria; abundant serum antibody responses without cellular immune responses occured for i.m. injection and antibody responses could be elicited by i.m. boosting of animals primed by oral vaccination. Patterns of cellular immune responses to Salmonella vaccines in rhesus were similar to the previously described immune responses to low dose intrarectal inoculation with SIV; responses to low dose virus proved protective against subsequent intrarectal virus challenge and we are not testing the efficacy of Salmonellla against intrarectal virus challenge. Keywords AIDS, vaccine; Salmonella typhimurium; subunit; oral administration